Published in:
01-04-2009 | Original Article
Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia
Authors:
Rebecca Schüle, Elisabeth Brandt, Kathrin N. Karle, Maria Tsaousidou, Stephan Klebe, Sven Klimpe, Michaela Auer-Grumbach, Andrew H. Crosby, Christian A. Hübner, Ludger Schöls, Thomas Deufel, Christian Beetz
Published in:
Neurogenetics
|
Issue 2/2009
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Abstract
Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP. One sporadic patient showing HSP as well as optic atrophy carried a homozygous nonsense mutation. Compound heterozygosity was observed in a recessive family with a clinically pure phenotype. A heterozygous missense change segregated in a small dominant family. We also found a significant association of a known coding polymorphism with cerebellar signs complicating a primary HSP phenotype. Our findings suggest CYP7B1 alterations to represent a rather frequent cause of HSP that should be considered in patients with various clinical presentations.